Hepatitis A and B vaccination and public health

Summary.  The introduction and implementation of hepatitis B vaccination programmes in areas of high endemicity has been very stressful. However, this initial accomplishment has led to the reassessment of priorities in some countries which could undermine these early successes. Work still remains to be done to support and implement interventions that will bring us closer to the WHO goal and to the control of hepatitis B in the community at large. Hepatitis A vaccine strategy for immunizing toddlers is shifting to those countries with intermediate endemicity where increasing morbidity in adults is being observed. Accumulating evidence indicates that such programmes can result in impressive reductions in the incidence of hepatitis A by herd immunity. Monitoring of these populations to determine durability of protection will be important to avoid shifting the infection to the older age population, when symptoms are more likely to occur. National policies need to consider hepatitis A vaccination in the context of other public health priorities.     

A review of chronic hepatitis B epidemiology and management issues in selected countries in the Middle East

Experts from seven countries convened as a Specialist Panel for the Middle East to share information on practical issues relating to the epidemiology, diagnosis and management of chronic hepatitis B (CHB) infection. The Middle East is regarded as a region of high-to-intermediate epidemicity; however, infant vaccination programmes have successfully lowered the prevalence of hepatitis B infection in most countries to that of low-to-intermediate endemicity. Vaccine issues still to be addressed included improving coverage in some rural/poor communities, instituting hepatitis B vaccine at birth and providing vaccines for high-risk population groups. Hepatitis B infection in the Middle East primarily occurs as a result of perinatal infection, horizontal transmission between family members and transmission from injections. Blood transfusion services have broadly efficient screening programmes, but immunocompromised and haemodialysis patients are at risk. The cost of screening, monitoring and treating CHB influences practice in a number of Middle East countries, and there is a need for information on the most cost-effective options.     

Vaccination against hepatitis B: current challenges for Asian countries and future directions

AIMS: To review the current status of hepatitis B immunization programmes as well as future issues concerning hepatitis B immunization in Asian countries. METHODS: Pertinent literature was identified via in-house and MEDLINE (1980-99) searches and references cited in published articles. Articles within the Proceedings of the IX Triennial International Symposium on Viral Hepatitis and Liver Disease provided valuable state-of-the-art resource data. RESULTS: Chronic hepatitis B infection is responsible for 75-90% of primary hepatocellular carcinoma, one of the 10 most common cancers worldwide. Hepatitis B and its chronic sequelae can potentially be eradicated through vaccines that have been shown to be 95-99% efficacious in preventing development of the disease or the carrier state in immunized infants. Approximately 75% of the world's hepatitis B carriers live in Asian countries wherein wide variations in immunization strategies exist. Vaccination programmes in hyperendemic Asian countries have elicited decreases in the incidence of acute and chronic infections as well as a decrease in chronic carriers in the unvaccinated population. Decreases in the incidence of hepatocellular carcinoma have been recorded in Taiwan and Singapore after at least 10 years of universal hepatitis B immunization programmes. CONCLUSIONS: In Asian countries currently without nationwide hepatitis B programmes, utilization of the existing vaccination infrastructure for administration of other World Health Organization Expanded Programme on Immunization vaccines will provide the most economical and efficient means of administration of the hepatitis B vaccine.     

Prospects for hepatitis B virus eradication and control of hepatocellular carcinoma

Hepatitis B virus infection is the most common cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. In areas hyperendemic for HBV infection, the related complications occur mostly during adulthood. However, nearly half of all primary infection in chronic carriers occurs in the perinatal period through maternal transmission, the other half arising from horizontal transmission mainly through intrafamilial spread or injection using unsterilized needles. A universal vaccination programme is better than immunization for at-risk groups. Hepatitis B vaccination should be integrated into the Expanded Programme on Immunization in children. Universal immunization against hepatitis B virus has proved to be effective in reducing the hepatitis B carrier rate to one-tenth of the prevalence before the vaccination programme in highly endemic areas, and the incidence of hepatocellular carcinoma in children has also been shown to be significantly reduced. Continued efforts to implement universal vaccination programmes worldwide will very likely reduce the incidence of hepatitis B virus-related diseases, particularly liver cirrhosis and hepatocellular carcinoma.     

Enhanced surveillance of hepatitis B in the EU, 2006–2012

Robust epidemiological information on hepatitis B is important to help countries plan prevention and control programmes and evaluate public health responses to control transmission. European Centre Disease Prevention and Control (ECDC) introduced enhanced surveillance of hepatitis B at EU/EEA level in 2011 to collate routine surveillance data from national notification systems. Analysis of the data collected for the years 2006–2012 shows a high burden of hepatitis B across Europe with 110 005 cases reported over the period with the majority of these cases being chronic infections. The most commonly reported routes of transmission in acute cases included heterosexual transmission, nosocomial transmission, injecting drug use and transmission among men who have sex with men. Mother‐to‐child transmission was the most common route reported for chronic cases. Trends over time were difficult to analyse as national reporting practices changed, but data suggest a downward trend in acute cases, which probably reflects the impact of the widespread implementation of vaccination programmes. Notifications of chronic infection varied across countries and showed discrepancy with the expected results based on findings from recent prevalence surveys. This indicated that notifications mirror local testing practices rather than real occurrence of disease. Improving the quality of the data and considering reported notifications alongside other data sources, such as local screening practices and vaccination policies, will improve the utility of the data.     

Hepatitis B surface antigenaemia following vaccination with a combined vaccine against hepatitis A and B

Summary.  We report a case of transient hepatitis B surface antigenaemia (HBsAg) following vaccination with a combined vaccine against hepatitis A and B in healthy adults. This phenomenon has been observed following administration of recombinant hepatitis B (monovalent) vaccine, mainly in newborns or dialysis patients. Reports on healthy adults are much less frequent and mostly concern blood donors. The frequency of its occurrence is largely unknown but its duration does not exceed 28 days. It is not detected by all available assays. It is caused by a passive tranfer of antigen by vaccination, and not by viral replication; hence there is no risk for vaccination-induced infection. An important implication resulting from our findings is that the results of HBsAg assays should be interpreted according to the time elapsed since the last administration of a recombinant monovalent vaccine against hepatitis B or a combined vaccine against hepatitis A and B.     

Implementation of Vaccination in Patients with Cirrhosis

Vaccination for hepatitis A, hepatitis B, pneumococcus, and influenza in patients with chronic liver disease is recommended. Our purpose was to determine the degree of adherence to these recommendations in cirrhotics presenting for liver transplantation evaluation. Our sample consisted of 105 patients presenting for evaluation for liver transplantation. Data were obtained by medical record review and patient interview. The age of the patients was 52 ± 9 years (mean ± sd) and the Child-Pugh score was 9 ± 2. Twenty-nine patients had natural immunity for hepatitis A. Of the remaining 76, 20 (26.3%) received vaccine. Of the 89 patients without evidence of prior exposure to hepatitis B, 23 (25.8%) received vaccine. Pneumococcal and influenza vaccination was performed in 36 (34%) and 58 (55%) respectively. In conclusion, vaccination for viral hepatitis, pneumococcus, and influenza not being consistently performed. Public health efforts aimed at raising awareness about implementing vaccination in these patients are strongly encouraged.     

hepatitis B virus burden in developing countries

Hepatitis B virus(HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.     

Should hepatitis B vaccination be introduced into childhood immunisation programmes in northern Europe?

Infection with hepatitis B causes between 500,000 and 1.2 million deaths per year worldwide, and is the leading cause of liver cancer. Over 12 years ago, WHO recommended that universal childhood hepatitis B vaccination be implemented globally. Despite this, Denmark, Finland, Iceland, Ireland, the Netherlands, Norway, Sweden, and the UK have yet to implement such a policy and instead currently adopt an "at-risk" strategy. Although all eight countries are classed as having low endemicity, factors such as increased travel and integration of immigrant communities are increasing the number of at-risk individuals in these countries. Considering the difficulty in identifying all at-risk individuals, and the lack of effectiveness of at-risk vaccination on reducing the overall incidence of hepatitis B, we recommend that these countries reassess their hepatitis B prevention strategies. Universal vaccination against hepatitis B is the only way to eliminate the major public-health impact of this disease.     

Differences in hepatitis A seroprevalence among geographical regions in Turkey: a need for regional vaccination recommendations

Summary.  Hepatitis A is a worldwide vaccine-preventable infection. Recommendation of vaccination depends on the endemicity of the disease. The World Health Organization recommends universal hepatitis A vaccination in intermediate areas; however, there is no need of mass vaccination in high and low endemicity regions. Therefore, most of the countries are using a vaccination policy according to the endemicity characteristic representing the whole of the country. The endemicity of this infection varies due to sanitary and hygiene conditions and socioeconomic differences among the countries and in various regions of the same country. A sample of 1173 persons between the age of 0 and 91 years from nine randomly selected medical centres from five different geographical centres of Turkey were tested for the level of anti-hepatitis A virus (anti-HAV) immunoglobulin-G antibodies using an enzyme-linked immunosorbent assay. The overall prevalence of anti-HAV antibodies was 64.4% (1142/1173). While the rate of sero-positivity was over 80% in the 5–9 age group and more than 90% after 14 years of age in south-eastern and eastern regions, it was lower than 50% at the age of 5–9 years in central and western regions and remains under 80% in those areas. We conclude that the differences observed in HAV sero-positivity among various geographical regions in Turkey support a universal HAV immunization policy for children currently living in regions of intermediate endemicity.     

Hepatitis B Vaccination: A Historical Overview with a Focus on the Italian Achievements

Vaccination is the most effective way to control and prevent acute and chronic hepatitis B, including cirrhosis and HCC, on a global scale. According to WHO recommendations, 190 countries in the world have introduced hepatitis B vaccination into their national childhood immunization programs with an excellent profile of safety, immunogenicity, and effectiveness. Following vaccination, seroprotection rates are close to 100% in healthy children and over 95% in healthy adults. Persistence of anti-HBs is related to the antibody peak achieved after vaccination. The peak is higher the longer the antibody duration is. Loss of anti-HBs does not necessarily mean loss of immunity since most vaccinated individuals retain immune memory for HBsAg and rapidly develop strong anamnestic responses when boosted. Evidence indicates that the duration of protection can persist for at least 35 years after priming. Hence, booster doses of vaccines are currently not recommended to sustain long-term immunity in healthy vaccinated individuals. In Italy, vaccination against hepatitis B is met with success. In 2020, Italy became one of the first countries in Europe to be validated for achieving the WHO regional hepatitis B control targets.     

Current evidence on the management of hepatitis B in pregnancy

Hepatitis B virus(HBV) infection is one of the main public health problems across the globe,since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries,nevertheless the infection is still widespread also in its active form. In the areas of high endemicity(prevalence of hepatitis B surface antigen positivity 7%),mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore,the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy,with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.     

Vaccination against hepatitis A and B: developments, deployment and delusions

PURPOSE OF REVIEW: Current issues in immunization against hepatitis A and B are discussed, including the need to abandon risk-based approaches in favour of universal vaccination, the use of combined hepatitis A and B vaccines and multivalent vaccines, the development of third-generation triple antigen hepatitis B vaccines and polyvalent vaccines. RECENT FINDINGS: The emergence of hepatitis B surface antigen mutants remains a concern in diagnostic work and immunoprophylaxis and horizontal transmission of the G145R variant stresses the need for surveillance programmes. The more recent and unfounded concerns about the safety of hepatitis B vaccines are noted. Innovative approaches to vaccine production including DNA vaccines and the expression of hepatitis B antigen components in plants (edible vaccines) are reviewed. SUMMARY: This review describes further evidence to support the introduction of universal immunization against hepatitis B in those countries where this has yet to be implemented. Immunization programmes will continue to evolve to include the administration of polyvalent vaccines in order to best protect populations against infectious diseases.     

Toward elimination and eradication of hepatitis B

Hepatitis B virus (HBV) causes important human health problems. It has infected one-third of the world's population and approximately 360 million people are chronic carriers. Worldwide, 0.5–1.2 million deaths are attributed to HBV infection annually. Therefore, global control of HBV infection is important. HBV infection can be intervened by interrupting routes of transmission, treating the chronically infected, and preventing the susceptibles with immunoprophylaxis. All these measures are effective. Nevertheless, although pegylated interferons or nucleos(t)ide analogs are effective for the treatment of chronic hepatitis B, chronic carriage of HBV is not easy to eliminate, as revealed by the frequent persistence of hepatitis B surface antigen, despite satisfactory responses to these treatments. On the other hand, hepatitis B vaccination has been shown to preclude HBV infection effectively. This is particularly true for pre-exposure prophylaxis. Worthy of note is the universal vaccination of newborn infants. This is the most effective means of preventing HBV infection, especially for those born to HBV carrier mothers. To eliminate and eradicate hepatitis B, first, HBV in the chronically infected should be eradicated or strongly and efficiently suppressed, so that the infection does not spread rampantly. Second, all the transmission routes should be interrupted. Lastly, but most effectively, is to immunize all susceptibles. The difficulties and possible solutions of each approach are discussed. In conclusion, the existing means to prevent and treat HBV infection render our goal toward eliminating and eradicating hepatitis B possible, although it will take much time and effort to achieve this objective.     

Has the time come to control hepatitis A globally? Matching prevention to the changing epidemiology

Summary.  For the first time a global meeting on hepatitis A virus (HAV) infection as vaccine preventable disease was organized at the end of 2007. More than 200 experts from 46 countries gathered to investigate the changing global HAV epidemiology reflecting the increasing numbers of persons at risk for severe clinical disease and mortality from HAV infection. The benefits of childhood and adult hepatitis A (HepA) vaccination strategies and the data needed by individual countries and international health organizations to assess current HepA prevention strategies were discussed. New approaches in preventing HAV infection including universal HepA vaccination were considered. This introductory paper summarizes the major findings of the meeting and describes the changing epidemiology of HAV infections and the impact of HepA vaccination strategies in various countries. Implementation of HepA vaccination strategies should take into account the level of endemicity, the level of the socio-economic development and sanitation, and the risk of outbreaks. A stepwise strategy for introduction of HepA universal immunisation of children was recommended. This strategy should be based on accurate surveillance of cases and qualitative documentation of outbreaks and their control, secure political support on the basis of high-quality results, and comprehensive cost-effectiveness studies. The recognition of the need for increased global attention towards HepA prevention is an important outcome of this meeting.     

Hepatitis B vaccine boosters: Is there a clinical need in high endemicity populations?

The Steering Committee for the Prevention and Control of Infectious Diseases in Asia recently conducted a survey of primary-care physicians in Asia, which revealed that many physicians administer boosters in their clinical practice and that there is considerable variation and uncertainty among physicians regarding this practice. This paper serves as a response to physicians' uncertainties by reviewing the literature regarding the administration of hepatitis B vaccine boosters in high endemicity areas and presenting the Steering Committee's guidelines for booster administration. While there are few data to support a need for routine hepatitis B vaccine boosters as a public health measure, they help to provide reassurance of immunity against breakthrough infection in certain risk groups. In clinical practice, primary-care physicians must exercise their judgment regarding the need for booster vaccination on an individual basis. This paper examines the available literature on the administration and value of hepatitis B vaccine boosters, explores the differences between the public health approach and clinical practice, and provides guidelines for those who use boosters in high endemicity Asian populations. Relevant articles were identified through searches of MEDLINE (1975-2003) and the Cochrane Library, using 'hepatitis B' and 'booster' as primary search terms. Guidelines for those who decide to administer hepatitis B vaccine boosters include: boosting approximately 10-15 years after primary vaccination; boosting rather than not when monitoring of antibody levels is not feasible; boosting immunocompromised patients when the antibody to hepatitis B surface antigen titer falls below 10 mIU/mL; and boosting healthcare workers based on the endemicity of the particular country.     

Hepatitis B vaccine boosters: Is there a clinical need in high endemicity populations?

The Steering Committee for the Prevention and Control of Infectious Diseases in Asia recently conducted a survey of primary-care physicians in Asia, which revealed that many physicians administer boosters in their clinical practice and that there is considerable variation and uncertainty among physicians regarding this practice. This paper serves as a response to physicians' uncertainties by reviewing the literature regarding the administration of hepatitis B vaccine boosters in high endemicity areas and presenting the Steering Committee's guidelines for booster administration. While there are few data to support a need for routine hepatitis B vaccine boosters as a public health measure, they help to provide reassurance of immunity against breakthrough infection in certain risk groups. In clinical practice, primary-care physicians must exercise their judgment regarding the need for booster vaccination on an individual basis. This paper examines the available literature on the administration and value of hepatitis B vaccine boosters, explores the differences between the public health approach and clinical practice, and provides guidelines for those who use boosters in high endemicity Asian populations. Relevant articles were identified through searches of MEDLINE (1975–2003) and the Cochrane Library, using 'hepatitis B' and 'booster' as primary search terms. Guidelines for those who decide to administer hepatitis B vaccine boosters include: boosting approximately 10–15 years after primary vaccination; boosting rather than not when monitoring of antibody levels is not feasible; boosting immunocompromised patients when the antibody to hepatitis B surface antigen titer falls below 10 mIU/mL; and boosting healthcare workers based on the endemicity of the particular country.     

Hepatitis B immunisation in travellers: poor risk perception and inadequate protection

OBJECTIVES: A survey of European travellers was conducted during 2006 to determine travellers' immunisation status and risk for exposure to hepatitis B while travelling. DESIGN: A first telephone (Omnibus) survey established the prevalence of travel in the previous five years as well as demographic profile of travellers amongst the general population. A second online survey targeted travellers to moderate or high hepatitis B endemicity countries, using data from the first survey to ensure a final sample representative of the travelling population in each country. Self-reported vaccination status and participation in activities/situations at high risk of exposure to hepatitis B were recorded. PARTICIPANTS: A total of 5948 interviewees participated in the first (Omnibus) survey and 4151 travellers completed the online survey. SETTING: Belgium, Italy, Finland, Germany, Netherlands, Spain, Sweden and UK. RESULTS: Only 15% of 4151 travellers to endemic countries recalled specifically receiving hepatitis B vaccination. Fifty-one percent of travellers to endemic countries visited a health care professional (HCP) before travelling. Of these, 54% did not receive any hepatitis B vaccination. Fifty percent of all respondents had never discussed risk factors for hepatitis B infection with a health care professional. Altogether, 1 in 4 travellers were at increased risk for exposure to hepatitis B due to hospitalisation, sexual activity or body piercing/tattooing amongst others. Three percent of travellers to high risk destinations were health tourists of which 65% did not recall being vaccinated against hepatitis B. CONCLUSION: Compared to a previous survey, this follow on survey 7 years later indicates the risk of exposure to hepatitis B has increased, but not hand-in-hand with the protection of travellers against hepatitis B through vaccination: travellers to at risk destinations continue to be unvaccinated against hepatitis B, including those who visit health care practitioners prior to travelling. Advice regarding hepatitis B immunisation for travel is received infrequently and travellers remain unaware of the risks of hepatitis B associated with travel. Many high risk situations are not predictable prior to travel, supporting an all-inclusive approach to hepatitis B vaccination in travellers.     

Seroepidemiology: an underused tool for designing and monitoring vaccination programmes in low‐ and middle‐income countries

Seroepidemiology, the use of data on the prevalence of bio‐markers of infection or vaccination, is a potentially powerful tool to understand the epidemiology of infection before vaccination and to monitor the effectiveness of vaccination programmes. Global and national burden of disease estimates for hepatitis B and rubella are based almost exclusively on serological data. Seroepidemiology has helped in the design of measles, poliomyelitis and rubella elimination programmes, by informing estimates of the required population immunity thresholds for elimination. It contributes to monitoring of these programmes by identifying population immunity gaps and evaluating the effectiveness of vaccination campaigns. Seroepidemiological data have also helped to identify contributing factors to resurgences of diphtheria, Haemophilus Influenzae type B and pertussis. When there is no confounding by antibodies induced by natural infection (as is the case for tetanus and hepatitis B vaccines), seroprevalence data provide a composite picture of vaccination coverage and effectiveness, although they cannot reliably indicate the number of doses of vaccine received. Despite these potential uses, technological, time and cost constraints have limited the widespread application of this tool in low‐income countries. The use of venous blood samples makes it difficult to obtain high participation rates in surveys, but the performance of assays based on less invasive samples such as dried blood spots or oral fluid has varied greatly. Waning antibody levels after vaccination may mean that seroprevalence underestimates immunity. This, together with variation in assay sensitivity and specificity and the common need to take account of antibody induced by natural infection, means that relatively sophisticated statistical analysis of data is required. Nonetheless, advances in assays on minimally invasive samples may enhance the feasibility of including serology in large survey programmes in low‐income countries. In this paper, we review the potential uses of seroepidemiology to improve vaccination policymaking and programme monitoring and discuss what is needed to broaden the use of this tool in low‐ and middle‐income countries.     

Evidence of protection against clinical and chronic hepatitis B infection 20 years after infant vaccination in a high endemicity region

Summary. Vaccination against hepatitis B virus (HBV) immediately after birth prevents neonatal infection by vertical transmission from HBV carrier mothers. There is an ongoing debate whether infant vaccination is sufficient to protect against infection when exposed to HBV later in life. We studied 222 Thai infants born to HBsAg ?/+ and HBeAg ?/+ mothers who were vaccinated with recombinant hepatitis B vaccine at 0‐1‐2‐12 months of age. A subset of 100 subjects received a booster dose at age 5 years. Blood samples collected yearly for 20 years were examined for anti‐HBs antibodies and serological markers of hepatitis B infection (anti‐HBc, HBsAg, and in selected cases HBeAg, anti‐HBe, HBV DNA). During the 20‐year follow‐up, no subject acquired new chronic HBV infection or clinical hepatitis B disease. During the first decade, possible subclinical breakthrough HBV infection (anti‐HBc seroconversion) was only observed in subjects born to HBsAg +/HBeAg + mothers (6/49 [12.2%]). During the second decade, breakthrough HBV infections were detected in all groups (18/140 [12.8%]). Increases in anti‐HBs concentrations that were unrelated to additional HBV vaccination or infection were detected in approximately 10% of subjects in each decade. Primary infant vaccination with a recombinant hepatitis B vaccine confers long‐term protection against clinical disease and new chronic hepatitis B infection despite confirmed hepatitis B exposure. ( http://www.clinicaltrials.gov NCT00240500 and NCT00456625)